Inhibition of deoxyhemoglobin S gelation by noncovalent modifiers such as penylalanine is one strategy for potential therapeutic intervention of sickle cell anemia. Several synthetic ring substituted and other phenylalanine analogs have been tested for their inhibitory potential using equilibrium solubility and kinetic assays of sickle hemoglobin gelation. Ring substituted compounds such as o-methyl phenylalanine and p-aminophenylalanine retained the inhibitory effect similar to phenylalanine. Compounds such as m-nitrophenyl-alanine and o-nitrophenylalanine methyul ester had no inhibitory effect of deoxyhemoglobin S gelation. The stereospecific interaction of these inhibitors with hemoglobin is being studied by X-ray diffraction/difference Fourier methods using co-crystalization of these and similar compounds with R state and T state hemoglobins in several solvent systems.